Over the past few years, the incidence of Clostridium difficile infections has risen in the US, and 14,000 people have died from the persistent diarrhea this bacteria causes. Some patients who haven’t been cured by antibiotics have turned to “fecal transplants” – the introduction of a healthy person’s feces into a patient’s digestive system – with, according to case reports and news stories, great success. Now, the New England Journal of Medicine has published results of a randomized clinical trial of the treatment. Of 16 C. diff sufferers given fecal transplants, 15 were cured

Most of us carry thousands of strains of bacteria on and in our bodies, and evidence is mounting our collections of microbes (or microbiomes) perform important functions that keep us healthy. Antibiotics can kill off beneficial bacteria as well as pathogenic ones, and many C. diff sufferers develop the infection after a course of antibiotics. In most sufferers, additional antibiotics can cure the infections, but around 20% of patients relapse. The idea behind a fecal transplant is that it can re-populate the gut with good bacteria that keep C. diff in check. (For more on the evolving knowledge of the microbiome, check out Michael Specter’s recent New Yorker story.)

The Clinical Trial
The study by Els van Nood et al and conducted at the Academic Medical Center in Amsterdam involved 43 patients (41 of whom completed the study protocol) who’d had a relapse of C. diff infection after a course of the antibiotics vanomycin or metronidazole. The primary endpoint was cure of C. diff infection, without relapse, within 10 weeks following the start of treatment.

Sixteen patients were assigned to get fecal infusions following a 4- or 5-day course of vanomycin and a bowel lavage (or “intestinal wash,” in the New York Times article about the study). For the control groups, 13 patients got a 14-day course of vanomycin, and another 13 got a 14-day course of vanomycin followed with a bowel lavage on day four or five. “Bowel lavage was incorporated to reduce the pathogenic bowel content, facilitating colonization of healthy donor microbiota” in the fecal infusion treatment group, the researchers explain, and the third treatment group also got it to test the unlikely possibility that the intestinal washing itself can cure C. diff infections.

The fecal infusions consisted of feces from healthy donors diluted with saline, strained, and administered through a tube running through the nose to the small intestine. Researchers used a lengthy process to create a pool of healthy feces donors; it involved repeated health questionnaires, screening of feces for parasites and pathogenic gut bacteria, screening of feces for antibodies to HIV and many other diseases. Feces were collected and transported to the hospital on the day of the infusion. Researchers ended up using feces from 15 donors.

The results were striking: Of the 16 patients who got fecal infusions, 13 were cured after the first infusion and another two were cured after receiving a second infusion from a different donor – adding up to 15 out of 16, or 94% of this group’s members being cured. (To be cured, a patient had to have had three negative stool tests for C. diff toxin, and the cure adjudication committee members were blinded to treatment group assignments.) The cure rates in control groups were much lower: 4 of 13 (31%) for those getting vanomycin only, and 3 of 13 (23%) for those getting vanomycin plus bowel lavage. Most patients in both control groups experienced relapses.

Because so many of the control-group patients had relapses, the study’s data safety and monitoring board advised that the study be ended early. Eighteen of the patients experiencing relapses then received fecal infusions, and 15 of them were cured.

The researchers also studied the microbiota in nine patients prior to their treatment with fecal infusion, and found it to the diversity of microbes to be low. The diversity increased during follow-up, and the researchers report, “In eight patients for whom samples were available, the diversity of fecal microbiota remained undistinguishable from that of the donor during follow-up.” This lends support to the idea that the mechanism by which fecal infusions cure C. diff is re-establishment of a healthy microbiome.

Prospects for future treatment
The Boston Globe’s Carolyn Y. Johnson gives a snapshot of the current spotty use of fecal treatments for persistent C. diff infections:

Since the procedure was described by a Colorado medical team that used the technique in 1958, hundreds of success stories have accumulated in the medical literature and many hospitals have begun trying the procedure in an effort to control the growing public health threat of C. difficile. In New England, a gastroenterologist at the Women’s Medicine Collaborative in Providence has done 90 fecal transplants; at Massachusetts General Hospital, 10 children and a handful of adults have been treated; and at New England Baptist Hospital, 27 patients have received donor feces.

Having a clinical trial published in the NEJM will probably increase doctors’ willingness to consider using fecal infusions, and Johnson reports that more research on the procedure – including its use in patients with Crohn’s disease or inflammatory bowel disease – is underway. But, in Denise Grady’s New York Times article about the Dutch study, a doctor sounds a note of caution about a potential FDA barrier to more widespread adoption:

Dr. Lawrence J. Brandt, a professor at the Albert Einstein College of Medicine in New York, said that the Food and Drug Administration had recently begun to regard stool used for transplant as a drug, and to require doctors administering it to apply for permission, something that he said could hinder treatment.

In her piece, Johnson points out that “a lack of consensus about how to select and screen donors for infectious diseases” has been one obstacle to greater use of fecal infusions. One answer to that comes from doctors in Ontario, Canada, who’ve developed a brilliantly named synthetic stool called RePOOPulate. NPR’s Michaeleen Doucleff explains:

[Infectious disease specialist Elaine] Petrof and her team took a stool sample from a healthy, 40-year-old woman, who hadn’t taken antibiotics in 10 years.

Microbiologist Emma Allen-Vercoe, who invented the Robogut [a mechanical device that mimics the conditions in your colon], grew the bacteria from her stool and then sequenced the bugs’ DNA to figure which species were present. Using her clinical experience, Petrof selected 33 bacteria that she knew were healthy. The result was an opaque mixture of bacteria, which Allen-Vercoe describes as a “vanilla milkshake.” Really.

Petrof then put the bacterial cocktail into the intestines of the two patients during colonoscopies.

The new bacteria slowly grew in the patients’ guts and pushed out the toxic C. difficile. Both patients eventually stopped having diarrhea, and the transplanted bacteria were still present six months after the procedure.

Having a uniform, lab-produced bacteria could help researchers study the use of bacterial infusions by different administration routes and for different conditions (e.g., if it turns out that you can swallow a capsule rather than getting a tube down your nose, that would be great). It would probably also be easier for the FDA to approve the use of such a standardized product, rather than requiring any doctor treating C. diff patients to recruit and monitor the health of fecal donors.

Given how quickly bacteria are evolving resistance to the antibiotics we rely on, it’s helpful to have a new prospect on the horizon for treating infections.

Comments

The Scienceblogs front-page summary of this implies that bowel lavage is an essential part of the treatment, but in people who were treated only with antibiotics, it had – at the very best – no benefit. Since this procedure is undoubtedly unpleasant and with the potential for injury, it would be good to test whether it adds any value to fecal transplant, rather than simply assuming that customary invasive procedures must be necessary.

My uncle used the real deal -not fake poop…. it pretty much saved his life. Spread the word on fecal transplants! You don’t always need drugs to get healthy… check out my advocacy blog at fecaltransplant.info or www dot fecaltransplant dot info

According to the following website http://www.fecalmicrobiotatransplant.com , Professor Borody of Australia, a 25+ year pioneer of FMT, treated three patients for constipation as a result of multiple sclerosis. As an unexpected side effect in all three of them, their MS symptoms reversed and have remained in remission for many years (one over 15 years)! Amazing stuff! There are lots of other case studies of a wide range of diseases and ailments. Great video on this site also of him explaining the treatment for c-diff.

I work with the elderly and watch them go through course after course of antibiotics while they try to fight a noscomial C diff infection. I would love to participate in a standardized trial that would give my patients an opportunity to benefit from this therapy . Personally I think the best route is via low volume enema , even if it requires more than one treatment. Positioning can always be used to facilitate travel through the colon. As far as donors go- I suppose a family member living in the same household would be optimal but lack of a family member willing to donate should not be limitation.

I have been suffering from chronic diarrhea for over a year, with the last six months of my life totally affected by the condition, i.e, mapping out bathrooms, turning down social events, depression, etc. I learned about fecal transplant just three days ago, which is suprising because I search the internet everyday for information on my condition, but had never come across it before. I’ve been to numerous doctors and had all lab work done, everything tests normal. The gastro I saw last month started me on Flagyl, and I took two rounds, the first ten days and the second eight days. Had terrible side effects, but was desperate to get better. After the last round, I found the article on FTT. The second day after completing the second round of Flagyl (which I believe was still not working, as my symptoms were still present), I stayed home and made a mixture of my husband’s feces and saline water. I took two doses of immodium about one hour prior to starting the transplant. I introduced a small amount in my rectum via an enema. It was difficult to do, and I had to water it down a couple of times to get the right consistency. I had some cramping, and had to run to the toilet and defacate after administering it the first two times. The third time I did heavy breathing throughout the cramping and urge to defacate, and I was able to stay in bed. In total I probably administered only a few ounces of my husband’s feces into my rectum. I stayed in bed for a continuous 5 hours, and then got up and bathed, washed the bed linens, etc. I felt a little weird all day, like I had gone to the hospital for an outpatient procedure. I took it easy all day. The next day I woke up and felt very normal. I had one normal bowel movement. Today is the second day and I feel just like yesterday. I truly believe FTT has worked for me, and I want to tell the world about it. It is truly miraculous!

I was very ill with Crohn’s for years and finally tried Sky Curtis’s protocol for doing fecal transplants at home. After years of suffering, her treatment saved me! I have no more symptoms! I bought her guidebook from http://www.fecaltransfusions.com. No one needs to suffer any longer with this terrible disease. There’s hope!

I have had c diff now for two years almost three and have been treated with metro and vanco fot tjat long only stoped twice. no change then i founf out that the doctots.wete wrong in givong me three hundred miligrams of morphine and immofium while undet treatmeny and it was constipating me which inturn kept toxins growing and now vanco is not working anymore eitjer causr of building immunitu. im now anorexic my orhans are.mow having problems i cant eat anytjing i keep loosing alot of mucus and blood and the province has said that o dont qualify gor fecal transplant due to the fact of my age being 32and its only for elderly and. tp ypung for surgery. all i do is lay lethargic on my bed ttrying to find someone who has tjis and has had treaent and who cam help save my life by opening their dpor so i can come get help from their succesful specialist who cam save my life. i have two girls tjat r going to loose tjeir mommy vety quiclly if i dont get help my heart rate is now flowing betwren forty and fifty and the muclea are give put now and i vant gey my meds in or my beya.blockers caise of tjis. if tjee is someone a doctor and a nice soul who will opem tjeir home to an angel and help save my kuds mom i will bless u in returm witj rent whatever is needed to show our appreciation. the provonce uere keeps telling me to keep taking vanco and yet ither g
ps r discriminatong me against them cause their not worling but only maling it worse now. i have candida high fever heat rash from fevers getting. so higj i go into seizures. pleae helpe someone or see f their doctor specialist will takey vase on pleasr email me back hod blless i dont have much longer to live grom anorexia andinfection now spreading

[…] Over the past few years, the incidence of Clostridium difficile infections has risen in the US, and 14,000 people have died from the persistent diarrhea this bacteria causes. Some patients who haven’t been cured by antibiotics have turned to “fecal transplants” – the introduction of a healthy person’s feces into a patient’s digestive system – with, according to case reports and news stories, great success. Now, the New England Journal of Medicine has published results of a randomized clinical trial of the treatment. Of 16 C. diff sufferers given fecal transplants, 15 were cured. (link) […]

As a patient I would never attempt fecal transplants own my own.There need to be more randomizes studies to prove the effectivess of stool transplant on patients with Crohns disease,a dangerous and life long predicament,very expensive and dangerous to treat.The drugs involved in the treatment have dire side effects.Patient with the disease will have multiple complications and surgeries through their life time.The NIH should be involved and testing for potential donors should be free.Insurance companies should be happy to trade the cost of testing donors,300 to 400 dollars versus the enormous cost of hospitalizations and surgical interventions.I am interested in knowing if any OFFICIAL studies are under way.